Rapid decay of averaged single-channel NMDA receptor activations recorded at low agonist concentration

The NMDA class of glutamate receptors have the unique property of binding some agonists, including glutamate, for a very long period of time. One manifestation of this is that brief (1 ms) application of glutamate (1 mM) produces a slowly decaying current, the major component of which has a time constant of approximately 200 ms. Application of glutamate at low concentrations allows identification of groups ('superclusters') of openings in the data record that probably correspond to a single period during which one or more molecules of glutamate are bound to the receptor, i.e. a single activation of the channel. The length of such superclusters is long on average (74 ms); the longest component of the distribution has a duration of approximately 300 ms, and comprises about 25% of the area. However, aligning many superclusters to obtain an average current reveals that the decay is mainly fast; the major component has a time constant of around only 5 ms. It is shown that incorporation of a distribution of first latencies (from the time of the jump to the first opening) can explain at least part of this discrepancy.